This work is attempting to delineate the origin of those cells in bone which are responsible for bony resorption in the normal bone remodeling sequence. Indirect evidence has shown the strong likelihood of origin of these cells outside the bone marrow, that is, from the circulation. The osteoclast precursor cell should be transferrable from one animal to another under appropriate conditions. It is known that the injection of spleen or bone marrow cells from an F-1 hybrid (donor) into an irradiated parent (recipient) will not lead to a host versus graft donor rejection reaction, but will allow the establishment of a line of cells in the recipient with surface markers different from those of the original recipient cells. By using available inbred strains of mice, their progeny and appropriate antisera against major H-2 surface histocompatibility antigens, it should be possible by immunofluorescent labelled markers to detect and identify donor cells. By these methods, the question of the origin of the osteoclast from circulating precursor cells may be resolved. In addition, attempts at defining subpopulations of circulating cells contributing to osteoclastogenesis are in progress.